The goal of this project in the Baltimore Longitudinal Study of Aging is to characterize the age-related changes in bone mass and body composition that have been demonstrated in both men and women. Age and sex related differences hormones, nutritional and physiological variables involved in bone turnover are important in elucidating changes in bone physiology in normal aging and disease. Specifically, the relationships of age and sex to changes in body composition, both as a marker of obesity and as a measure of the weight-bearing load on bone are important factors in bone status and rates of change. The most dramatic rates of change in bone mass occur at the menopause, and changes of body composition, bone mass, and bone markers and hormones are being investigated in 114 women aged 45-55 who have been recruited to the Baltimore Longitudinal Study of Aging as part of the perimenopausal cohort. The women, who were still menstruating, on entry to the study, are followed at 3month intervals as they traverse the menopause, and for two years since their last period. The studies will allow for the interpretation of the changes that occur prior to and mmediately around the time of the cessation of menses, changes that can only be appreciated in a prospective longitudinal study. Currently, 10-15 women are continuing to be studied. Cross-sectional studies suggest that the perimenopausal transition is associated with rapid decreases in serum levels of estrogen, followed by increases in those of FSH>LH, and that the estrogen changes are influenced by body fat mass. We evaluated the changes in follicle stimulating hormone (FSH), estradiol (E2), estrone (E1), E2/E1, and sex hormone binding globulin (SHBG) values at various intervals (-2 yrs, -1 yr, 0, +1 yr, and +2 yrs) referable to the onset of menopause, defined as the time of the first elevation in FSH levels to >30 mIU/ml. Longitudinal increases were found in circulating levels of FSH, and decreases in values for E2, E1, E2/E1, while SHBG did not change. The declines in E2 and E1 levels occurred concurrently and preceded the rise in FSH, although the decline in E2 was greater than that of E1. After adjustment for age at initial FSH>30, the levels of FSH were inversely related to BMI and total body fat as assessed by DEXA, whereas E2 and E1 were not independently related to either index of body fat. The relationships of these endocrine changes to perimenopausal alterations in fat, skeletal muscle and bone metabolism remain to be determined.